Key Findings
Oxylipins are oxidized metabolites of fatty acids that can be formed attached to phospholipid or when fatty acids are released from membrane phospholipids via phospholipase A2. These include eicosanoids, octadecanoids, and docosanoids. Obesity may be associated with increased levels of proinflammatory and vasoconstrictive eicosanoids and decreased levels of anti-inflammatory eicosanoids. Oxidative stress, inflammation, and altered hemodynamics in kidneys of obese individuals are associated with the onset of an emerging condition referred to as obesity related glomerulopathy (ORG). This study showed that LA and ALA oxylipins can be significantly altered by dietary intervention. Glomerulomegaly in the diet-induced obese rat was inversely associated with renal oxylipins derived from ALA, suggesting a possible protective effect of unique oxylipins from ALA.
ABSTRACT
Analysis of oxylipins derived from fatty acids may provide insight into the biological effects of dietary lipids beyond their effects on tissue fatty acid profiles. We have previously observed that diets with higher amounts of alpha linolenic acid (ALA; 18:3n3) are associated with reduced obesity-related glomerulopathy (ORG). Therefore, to examine the renal oxylipin profile, the effects of dietary linoleic acid (LA; 18:2n6) and ALA on oxylipins and renal phospholipid fatty acid composition, and the relationship between oxylipins and ORG, diet-induced obese rats displaying ORG were fed 8 different diets for 8 wk as follows (oil/oil equal combination of two oils) [shown as ALA/LA (in g) per 100 g oil]: canola/flax (20/18), canola (8/18), soy (9/53), high oleic canola/canola (5/16), high oleic canola (2/15), lard/soy (1/8), and safflower (0.2/73). Targeted lipidomic analysis by HPLC–tandem mass spectrometry revealed that LA and ALA oxylipins comprised 60percent of the total renal oxylipin profile examined. Of the greater than 60 oxylipins screened, only those derived either directly or indirectly from ALA were associated with less glomerulomegaly, indicative of reduced ORG progression. Both the amount and ratio of dietary LA and ALA influenced renal polyunsaturated fatty acids (PUFAs); in contrast, only fatty acid amount altered oxylipins derived from these fatty acids, but there was no apparent competition by LA or ALA on their formation. Dietary LA incorporation into renal phospholipids was higher than for ALA, but ALA oxylipin:ALA ratios were higher than the analogous LA ratios for select lipoxygenase reactions. This indicates that the effect of dietary ALA on renal oxylipins exceeded what was reflected in renal PUFA composition. In conclusion, dietary LA and ALA have differential effects on renal oxylipins and PUFAs, and ALA derived oxylipins are associated with renoprotection in this model of ORG. (Authors abstract)
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